Anti-BCMA heavy chain-only antibodies
Inventors
Force Aldred, Shelley • Trinklein, Nathan • Harris, Katherine E. • Dang, Kevin • van Schooten, Wim
Assignees
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Publication Number
US-12371505-B2
Publication Date
2025-07-29
Expiration Date
Abstract
Anti-BCMA heavy chain-only antibodies(HCAb) and disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat B-cell disorders characterized by the expression of BCMA.
Core Innovation
The invention provides anti-human B-Cell Maturation Antigen (BCMA) heavy chain-only antibodies (HCAbs). The disclosed HCAbs include a heavy chain variable region (VH) with defined CDR1, CDR2, and CDR3 sequences, including a shared CDR3 sequence corresponding to SEQ ID NO:19. The VH framework is defined by specified sequence identity thresholds to human VH frameworks provided in the disclosure.
The HCAbs are further characterized by sequence-defined embodiments that optionally include heavy-chain constant regions lacking CH1, together with variable region sequence constraints. The disclosure also describes VH framework definitions using specified CDR1/C5–C4 patterns and CDR2 variable formulas, while maintaining the defined CDR3 sequence. Different antibody formats and embodiments are described, including constructs that present the antibody as bispecific or multispecific antibodies and binding-domain constructs.
The disclosure also presents therapeutic and composition embodiments for targeting BCMA-expressing disorders. Pharmaceutical compositions and use cases are described for treatment of BCMA-expressing B-cell/plasma-cell disorders, including multiple myeloma and systemic lupus erythematosus. The document further describes polynucleotides, vectors, and cells comprising such polynucleotides, and includes CAR-T binding-domain constructs associated with BCMA binding and blocking activity.
Claims Coverage
The independent claim covers a heavy chain-only antibody binding human BCMA, defined by specific CDR sequences. Across the dependent claims, the coverage is narrowed and expanded by additional sequence identity constraints, specific VH sequence inclusion, structural constraint regarding CH1 absence, and additional embodiments in CAR-T format and genetic-material delivery embodiments via vectors.
Defined Cdr1, Cdr2, and Cdr3 sequences for BCMA binding
A heavy chain-only antibody binding to human BCMA comprising a heavy chain variable region comprising a CDR1 sequence comprising SEQ ID NO: 3, a CDR2 sequence comprising SEQ ID NO: 7, and a CDR3 sequence comprising SEQ ID NO: 19.
Vh framework with at least 95% sequence identity to a reference sequence
The heavy chain-only antibody comprises a heavy chain variable region comprising at least 95% sequence identity to SEQ ID NO: 48.
Specific Vh sequence inclusion
The heavy chain-only antibody comprises a heavy chain variable region comprising SEQ ID NO: 48.
Heavy-chain constant region without CH1
The heavy chain-only antibody includes a heavy chain constant region sequence when CH1 sequence is absent.
Car-t format for the heavy chain-only antibody
The heavy chain-only antibody from claim 1, formatted as a CAR-T construct.
Vector encoding the claimed polynucleotide
A vector includes the polynucleotide recited in claim 8.
Overall, the claims cover anti-human BCMA heavy chain-only antibodies defined by specific CDR1/CDR2/CDR3 sequence identities, optionally constrained to a defined VH framework sequence with at least 95% identity and optionally structured with heavy-chain constant regions lacking CH1. The claims also extend to CAR-T format embodiments and to vectors encoding the relevant polynucleotide.
Stated Advantages
Documented Applications
Treatment of BCMA-expressing B-cell/plasma-cell disorders, including multiple myeloma.
Treatment of BCMA-expressing B-cell/plasma-cell disorders, including systemic lupus erythematosus.
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